FGFR1 amplification heralds poor prognosis in SCCL

Dec 10 2012

By Joanna Lyford, Senior medwireNews Reporter

Amplification of the fibroblast growth factor receptor 1 (FGFR1) gene independently predicts poor outcomes in patients who have undergone resection of squamous cell lung cancer (SCCL), research shows.

The study, by Byoung Chul Cho (Yonsei Cancer Center, Seoul, Republic of Korea) and co-workers, also found that FGFR1 amplification was associated with cigarette smoking in a dose-dependent manner.

Taken together, these observations indicate that FGFR1 amplification is a "relevant therapeutic target" in SCCL, say Cho et al writing in the Journal of Clinical Oncology.

The researchers measured FGFR1 gene copy numbers in microarrayed tumor samples from 262 patients with SCCL. Overall, 13.0% of tumors showed FGFR1 amplification, defined a priori as those with nine or more gene copies.

When patients were divided according to the presence versus absence of FGFR1 amplification, several significant differences emerged. For instance, patients with FGFR1 amplification had significantly shorter disease-free survival (DFS; 26.9 vs 94.6 months) and shorter overall survival (OS; 51.2 vs 115.0 months) compared with patients without FGFR1 amplification.

In multivariate analysis that adjusted for gender, smoking status, pathologic stage, and adjuvant chemotherapy, FGFR1 amplification conferred a significantly increased risk for disease recurrence and death. Adjusted hazard ratios were 2.24 for DFS and 1.83 for OS.

A separate analysis found that the incidence of FGFR1 amplification was significantly higher in current and former smokers than in never-smokers, with frequencies of 28.9%, 2.5%, and 0%, respectively. Interestingly, there was evidence of a dose-response effect, such that the frequency of FGFR1 amplification rose from 5.2% in patients with 10-19 pack-years to 19.2% in those with 45 or more pack-years.

"This finding suggests that FGFR1 amplification is a major oncogenic aberration in SCCL that is induced by cigarette smoking," write Cho and co-authors. "According to our data, FGFR1 amplification is the only biomarker strongly related to smoking dose in patients with lung cancer."

They also note that, consistent with other studies, patients in this study with FGFR1 amplification benefited from adjuvant chemotherapy, whereas those without gene amplification did not.

"Concurrent genetic alterations in other regions of the genome associated with the DNA repair pathway may contribute to greater benefit from adjuvant chemotherapy," write the researchers. "Therefore, comprehensive genomic analysis will be needed to enhance treatment decisions for patients with resected SCCL."

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